Drug Properties: pKa, Half-Life, and Distribution

• pKa is the pH at which half the drug molecules are in ionized form
• Biological half-life of elimination (t1/2) is the time needed for a plasma concentration to decline by 50%
• Apparent volume of distribution (Vd) is the measure of a drug's distribution throughout the body
• A large Vd suggests extensive drug distribution in tissues
• A small Vd might occur when a drug binds significantly to plasma proteins
• Clearance (Cl) is the volume of blood cleared of a drug per unit time
• Bioavailability is the rate and extent to which a drug reaches systemic circulation and its site of action
• For a weak acid drug with a pKa of 4 in a medium of pH 3, the ratio of non-ionized to ionized drug is 10
• The Henderson-Hasselbalch equation allows calculating the ionization degree of acids and bases
• It also determines the proportion of non-ionized to ionized drug at a given pH
• Disulfiram inhibits aldehyde dehydrogenase, leading to a secondary effect
• Hepatic metabolism, biliary excretion, and urinary excretion are involved in elimination
• Gray baby syndrome occurs because of immature enzymatic processes
• Glucuronidation is affected

Pharmacokinetics

• Half-life is useful for determining total drug elimination time, time to steady state, and time for 50% elimination
• Large volume of distribution is the limiting factor for drug removal via extracorporeal methods (dialysis) in intoxicated patients
• Dose-response curves reveal safety margin and therapeutic index
• Pharmacokinetics studies how drug levels change over time in the body
• Pharmacokinetics involves drug processes and factors relating to the time evolution of drug in plasma and tissues
• Applying metrics such as T1/2, Vd, Cl allows therapeutic drug monitoring for efficacy
• Biotransformation reactions correspond to a non-synthetic classification of hydroxylation

Drug Action

• A drug portion bound to proteins is pharmacologically inactive
• Biological half-life predicts dosing intervals
• Bioavailability describes the fraction of drug that reaches systemic circulation unchanged
• Drug A at 5 mg producing effects of drug B at 500 mg makes drug A 100x more potent
• Biotransformation typically makes drugs less fat-soluble
• An agonist has affinity and efficacy

Drug Factors

• Bioavailability is 100% when a drug is administered intravenously
• First-pass effect influences bioavailability, including absorption rate, extraction ratio, half-life, and administration route
• Drugs binding receptors without activating them are antagonists
• An inhibitor not overcome by high agonist concentrations is a non-competitive antagonist
• A multicenter clinical trial to prove drug effectiveness on thousands of patients is a Phase III study
• Type 1 receptors affect ion permeability, applying to acetylcholine-nicotinic, GABA, glycine and glutamate
• Steroid hormones trigger slow responses compared to the above

Pharmacology of receptors

• Type 2 receptors use second messengers and are coupled to G proteins
• Gaba receptors bind to type 2 and 3 receptors, while insulin receptors don't bind to this type
• Alkaline diuresis manages weak acid intoxication
• Enhanced lipid/water partition coefficient of drugs infers ready membrane diffusion due to high lipophilicity
• Inactivation by 1st-pass hepatic metabolism negates oral administration
• Non ionized weak acid absorption happens in the small intestine
• Promethazine is an antihistamine with a pKa of 9.1
• Promethazine overdose excretion is accelerated by administering NH4Cl

Administration Issues

• Intramuscular and subcutaneous routes have more discomfort than other routes
• Aspirin (pKa 3.5) percentage in a stomach (pH 2.5) is 90% liposoluble form
• Alkalizing urine helps accelerate weak acid excretion
• Bronchoconstriction reversal of histamine happens with adrenaline
• Hydrophilicity/conjugation increases for the renal excretion of xenobiotics
• Hydroxylation initiates Phase 1 reactions
• The partition coefficient is the ability of dissolving organic compounds and solubility
• The ability to require preparations is the evaluation of animal studies

Drug-Dosing Considerations

• Digoxin half life is 1.6 days, so it takes 3.2 days to get serum lever to 1 ng/ml to remove the risk of toxicity
• The P450 cytochrome is essential for xenobiotic phase 1 liver monooxygenase metabolism
• Glucuronidation carries out liver elimination in phase 2
• The enzyme UDP-Glucuronosyl Transferase is related to the aforementioned
• The "dominant lethal" test includes treating a male with chemicals before mating and checking for abnormalities
• IV administration advantages include being indicated quickly, intravenously
• A Vd of 90L indicates the drug is concentrated in a specific tissue

Absorption and Transformation

• Biotransformation involves tolerance
• A drug that affects biological factors
• Sublingual delivery can bypass first-pass liver metabolism
• All factors except first-pass liver metabolism affect absorption
• Applying overdose equation increases non-ionized forms
• Henderson Hasselbalch reverses the effects above
• The ability to get outside of Intravascular happens intravascular
• Concentration gradients let drug to bind to receptors
• Passive diffusion allows drugs to pass through the cell membranes
• A half-life indicates steady state
• 3-5 vm achieve steady state
• An intoxicant has a large volume distribution
• Basic drugs can alkaline excretions given 7.5 or similar
• Phase 2 can make dosage

Potency, Agonists and Antagonists

• Drug B is most potent, it is the closest to the the Y axis, Drug C is potent but not efficacious
• Flumazenil is an antidote
• Clinical pharmacology is important to understanding and treating conditions
• Arsenic is a metabolism
• Receptor affinity is important to a complex
• Effects change from use
• Competitive antagonists curve from the agonist
• The reactions are catalyze
• Administer with appropriated dose
• Intratecal is beneficial due to direct placement
• 100 % Bioavailability is important

Agonists vs Antagonists

• Inhalents helps
• Response with generating with agonists
• Immuological is important

Drug Tolerance

• With two doses tolerance is important
• Pharm Clinical phase is important
• 10 is therapeutic dose and a dose for toxicity
• PH and intestial is important
• An antagonist is important
• Drugs bind to receptors
• A dose response is important
• Filtration happens but tubular absorption is also important

Drug Bioequivalence

• The drug administration is important
• The drug administration decreases
• They are equal in therapeutics
• Pharmacokinetics is important here, same concentration too
• You should have an effect in clinical trials
• Volume, UPP increase with all the parts listed
• H.T. has drugs

Additional Pharmacology

• Cit p-450 helps mutilation
• Receptor has affinity
• Side effects
• Absorption can increase
• Longer half can be good for prolonged
• Pharmicokinetics helps

Intoxication

• Syndromes are important to remember
• Charcoal is important, binds to the action
• Binds with many
• Drug responses change from receptor change
• Phases determine the efficiency
• Endoplasmic happens
• Integration and affinity
• Circulation
• Tolerance is a requirement for action
• Heart action
• Hereditary is important